The aim of this proposal is to improve the preclinical models available for endogenomorphic depression. The critical abnormal behaviors in this condition reflect disruptions of central pleasure or reward mechanisms. We will develop two types of model depression based on central reward disruption in rats: 1) Drug-induced - using inhibitors of amine synthesis to disrupt self-stimulation from specific brain areas; and 2) Drug-free using stress-induced suppression of motor activity and self-stimulation. Standard antidepressant procedures (tricyclic drugs, MAO inhibitors, electroshock) will be used before disrupting reward in the first type of model, and after disrupting reward in the second type. Preliminary studies by ourselves and others support this approach to the problem. These models are expected to clarify the effects of antidepressant treatments on reward functions and to provide improved screening procedures for new antidepressants.